Resumen:
Antimicrobial peptides have been developed based on plant-derived molecular scaffolds
for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa,
an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and
physicochemical-based strategies and designed four peptides derived from the primary structure of
Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named
Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1
sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine
(ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The
evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1
does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited
antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine
by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects.
These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis
highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic
simulations, we found that a pore is formed when multiple peptides are assembled in the membrane.
Whereas, some of them form secondary structures when interacting with the membrane, allowing
water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARSCoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the
design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.
